Glaucoma is a group of diseases that can lead to damage to the eye's optic nerve and result in blindness. The optic nerve connects the retina, the light-sensitive layer of nerve cells at the back of the eye, with the brain. A healthy optic nerve is necessary for good vision.
A common characteristic of glaucoma is increased intraocular pressure, excavation of the optic nerve head and gradual loss of the visual field. An abnormally high intraocular pressure (“IOP”) is commonly known to be detrimental to the eye, and there are clear indications that, in glaucoma patients, this probably is the most important factor causing degenerative changes in the retina. Unless treated successfully, glaucoma will eventually lead to blindness. Its course towards that stage is typically slow with progressive loss of the vision.
In the eye, a clear fluid called aqueous humor continuously flows into and out of a space near the front of the eye called the anterior chamber to nourish nearby tissue. The fluid leaves the anterior chamber through a meshwork of tissue at the angle where the cornea meets the iris. When everything functions correctly, the angle is open, pressure is normal, and inflow equals outflow.
Open-angle glaucoma is a form of glaucoma that gets its name because the angle where the cornea meets the iris is “open,” but the fluid passes too slowly out through the meshwork of tissue. Consequently, pressure rises until outflow again equals inflow, but now at a pressure that is elevated above normal. In many people, increased pressure inside the eye causes glaucoma (optic nerve damage). With early treatment to lower pressure one can often protect eyes against serious vision loss and blindness. Open-angle glaucoma is the most common form of glaucoma.
If the angle is closed and fluid cannot escape, however, continuous inflow causes the pressure to rise in the chamber. When this happens, a medical emergency is present that must be treated by surgery to open an exit passage for the aqueous humor.
Spironolactone, a nonspecific aldosterone receptor antagonist, was reported to lower IOP in glaucoma patients (Klin Monatsbl Augenheilkd, 176(3):445–6, (March 1980)). One other group has written about the possible role of aldosterone in glaucoma (Sevcik J., Pullmann R., Pitiova G., Cesk Oftalmol, 37(2):111–5, (March, 1981)).
Spironolactone, however, has antiandrogenic activity that can result in gynecomastia and impotence in men and weak progestational activity that can produce menstrual irregularities in women.
Accordingly, there is interest in development of additional active aldosterone receptor antagonists that do not interact with other steroid receptor systems such as glucocorticoid, progestin and androgen steroid receptor systems and/or that provide for a broader range of treatment. Preferably, such antagonists would be selective for aldosterone receptors.